All Subjects
- Healthy male and/or female of non childbearing potential subjects between the ages of
18 and 65 years, inclusive ('healthy' is defined as no clinically relevant
abnormalities identified by a detailed medical history, full physical examination,
including blood pressure and pulse rate measurement, 12 lead ECG, and clinical
laboratory tests).
- Body Mass Index (BMI) of 18 to 40 kg/m2 inclusive; and a total body weight >50 kg
(>110 lbs).
Subjects with Normal Renal Function (Group 1)
- Normal renal function (CLcr =>90 mL/min) during the screening period.
- Matched 1-to-1 to subjects in Group 2 with respect to age (+/-5 years), weight (+/-10
kg), gender, and race according to protocol.
Subjects with Severe Renal Impairment (Groups 2)
- Good general health commensurate with the population with chronic kidney disease.
- Severe renal impairment (CLcr
All Subjects
- Renal allograft recipients.
- Any condition possibly affecting drug absorption.
- 12 lead ECG demonstrating QTc >470 msec at screening.
- Urinary incontinence without catheterization.
- A positive urine drug screen.
- History of regular alcohol consumption.
- Treatment with an investigational drug within 30 days (or as determined by the local
requirement, whichever is longer) or 5 half lives preceding the first dose of study
medication.
- Pregnant or nursing females; females of childbearing potential, including those with
tubal ligation.
- Blood donation of approximately 1 pint (500 mL) within 56 days prior to dosing.
Subjects with Severe Renal Impairment (Groups 2)
- Subjects with any significant hepatic, cardiac or pulmonary disease (apart from stable
ischemic heart disease), or subjects who are clinically nephrotic.
- Subjects requiring hemodialysis.
- Subjects with strict fluid restriction (ie,
- Significant bleeding diathesis which could preclude multiple venipuncture.
- Use of food or drugs that are CYP3A4 inhibitors and inducers.
- Herbal supplements and hormone replacement therapy must be discontinued 28 days prior
to the first dose of trial medication
- Concurrent use of drugs that are CYP3A4 substrates with narrow therapeutic indices.